tbuckley/cabot-search huggingface dataset:
Abstract 14723: A Rare Case of Constrictive Pericarditis: Inflammatory Myofibroblastic Tumor
Authors: Muhammad Majid, Joshua Parker, Ashwin Kumar, Samia Mazumder, Alveena Syed, Allan L Klein
Journal: Circulation (2022)

Case Presentation: A 14-year-old female presented with a 3-week history of lower extremity edema, abdominal distension, fatigue, and dyspnea on exertion. Her examination was notable for an elevated jugular venous pulse, abdominal distension with hepatomegaly, and 2+ pitting edema in the bilateral lower extremities. Laboratory findings were within normal limits. EKG showed low-amplitude QRS and echocardiogram confirmed bi-atrial enlargement, a dilated and non-compressible IVC, dyskinetic interventricular septum, and elevated right atrial pressures. Chest computed tomography demonstrated mediastinal mass with findings of a 6.2 x 4-centimeter mass in the pre-vascular space, diffuse necrotic mediastinal lymphadenopathy, and constrictive pericarditis with associated congestive hepatopathy. Cardiac magnetic resonance imaging revealed significant enhancement in T2 STIR with severe circumferential delayed enhancement, diastolic bounce, and respirophasic shift. A right heart catheterization was pursued which revealed elevated filling pressures but preserved cardiac index. The patient underwent video-assisted thoracoscopic biopsy of the mass with an initial histologic diagnosis of inflammatory myofibroblastic tumor (IMT). She underwent radical pericardiectomy for symptom resolution. Discussion: IMT is composed of spindle cells mixed with infiltrates of varying numbers of inflammatory cells. Although IMT can present in any age group, most patients who develop IMT are in adolescence. IMT is incredibly rare and its etiology still remains unclear. It remains difficult to distinguish IMT from a malignant tumor on the basis of imaging. As a result, in most cases, a definitive diagnosis is made based on the histopathological findings from either a resected tumor or a needle biopsy. Management of IMTs presents a challenge as treatment protocols have not clearly been established; radical local excision of the tumor is the mainstay of treatment.
Abstract 14823: Atrial Electrical Substrates Associated With Atrial Fibrillation Drivers Analyzed With Real-Time Phase Mapping “ExTRa Mapping” in Patients With Persistent Atrial Fibrillation
Authors: Kosuke Nakasuka, Yukako Oishi, Marina Kato, Kento Mori, Toshihiko Goto, Yoshihiro Seo
Journal: Circulation (2022)

Introduction: Elucidation of the mechanism of atrial fibrillation (AF) will lead to improved catheter ablation outcomes. However, the electrical substrates on which AF drivers such as meandering rotors and multiple wavelets are likely to appear are still unclear. Methods: Twenty-nine patients (age 68±10 years, eight females) with persistent AF were included in this study. Real-time phase mapping (ExTRa mapping) was performed in the left atrium during AF. After that, electroanatomical mapping such as voltage and activation mapping with HD-grid catheter was performed after conversion to sinus rhythm with cardioversion. According to the nonpassively activated ratio (%NP: the ratio of the form of rotors and/or multiple wavelets to the recording time), the recorded three highest %NP (Active-area) and three lowest %NP areas (Passive-area) were collected in each subject. Electrical property and overlapping with the low-voltage zone (LVZ, voltage amplitude &lt;0.5mV) or mid-voltage zone (MVZ, 0.5-1.0mV) within these areas were assessed and compared between the Active- and the Passive-areas. Results: We analyzed a total of 87 Active- and 84 Passive-areas and the mean %NP were 61±8% and 13±8%, respectively. Signals with ≥4 fractionated components (fractionated electrograms) were seen significantly more in the Active-areas than in the Passive-areas (53% vs. 26%, respectively; p&lt;0.001, Figure A ). However, there was no difference in the conduction velocity (0.70±0.34m/s vs. 0.73±0.30m/s; p=0.577), mean voltage amplitude (1.78±1.54mV vs. 1.71±1.53mV; p=0.794) and coinciding with LVA/MVA (43% vs. 41%; p=0.785) between the Active- and the Passive-areas ( Figure B-D ). Conclusion: AF drivers tended to appear in the area with fractionated electrograms. High %NP areas partly overlapped, but not always coincided with LVA/MVA, as much as low %NP areas.
Abstract 14981: Stk25 Regulates Cell Survival in Both Human and Mouse Models of Myocardial Injury
Authors: Xiaokan Zhang, Bryan Wang, Trevor Nash, Jenny Rao, Lori Luo, Barry Fine, Gordana Vunjak-Novakovic
Journal: Circulation (2022)

Introduction: Dysregulation of cardiac kinases occurs in cardiovascular diseases including hypertrophy, remodeling and ischemia injury. Serine/threonine protein kinase 25 (STK25) is a stress response kinase and putative tumor suppressor that regulates cell survival and metabolism through several signaling pathways, including LATS/3HIPPO and mTOR pathways. Hypothesis: STK25 regulates cell survival, metabolism and cardiac function in human cardiomyocytes and animal injury models. Methods: CRISPR-Cas9 was used to generate a homozygous knockout (KO) of STK25 in induced pluripotent stem cell (iPSC) which were then differentiated into cardiomyocytes (iPSC-CMs). STK25 was quantified in human left ventricular tissue from heart failure (HF) patients. Stk25 KO mice were generated by CRISPR/Cas9 mediated genome engineering in C57BL/6J background. Role of STK25 in gene expression, cell proliferation/apoptosis, metabolism and cardiac function were characterized. Results: Gene set enrichment analysis (GSEA) of differential gene expression obtained by RNA-seq was used to identify upregulation of several growth and metabolism pathways in STK25KO iPSC-CMs including oxidative phosphorylation, mTORC1 signaling and myogenesis. In functional assays, STK25 modulated cell cycle progression, proliferation, hypoxia induced apoptosis, and mitochondrial respiration in iPSC-CMs. n a myocardial infarction model of cardiac injury, loss of Stk25 in vivo led to improvements in cardiac function, reduced cardiomyocyte death and diminished fibrosis. STK25 expression is increased in HF patients. Furthermore, loss of function mutations in STK25 were discovered in atrial myxomas, demonstrating STK25 altered regulation in human heart diseases. Conclusions: STK25 regulates cardiomyocyte survival in vitro and in vivo and is aberrantly regulated in both hearth failure and atrial myxomas.
Abstract 15400: A Call to Action for Mental Health Needs Amongst Patients Diagnosed With Critical Limb Ischemia: Insights From the Scope-Cli Registry
Authors: Kim G Smolderen, Mehdi H Shishehbor, Olamide Alabi, Robert Fitridge, Jeremy A Provance, Trissa Babrowski, Gaelle Romain, PETER A SOUKAS, Matthew C Bunte, Lindsey Scierka, Evy van Roij, Carlos Mena-Hurtado
Journal: Circulation (2022)

Introduction: Late stage PAD, or critical limb ischemia, is a devastating diagnosis where patients deal with pain, non-healing wounds, high rates of major amputation, and increased cardiovascular event risk. Previously, we have demonstrated that depression and perceived stress are prevalent in early-stage PAD and associated with adverse health status and mortality risk, but it is unclear what the mental health burden is in patients with late stage disease. Methods: In the ongoing 11-center SCOPE-CLI registry, patients with a new diagnosis of CLI (Rutherford 4-6) were enrolled and underwent assessments with the 8-item Patient Health Questionnaire (PHQ-8, range 0-24, score ≥10 denoting positive screen, scores 10-14 moderate, 15-19 moderately-severe, and 20-24 severe depressive symptoms) and the 4-item Perceived Stress Scale (PSS-4, range 0-15, scores ≥6 exceed normative population scores). Results: Between 01/2020 and 06/2022, we enrolled 184 patients with mean ages of 67.5±10.4 years, 20.1% were black, and 70.1% was male. A total of 22.3%, 71.7%, and 6.0% had Rutherford 4, 5, and 6, respectively. A total of 31.8% had a positive depression screen (mean 7.4±6.2), with rates being equally high across Rutherford categories. Somatic symptoms (sleep, appetite, fatigue) were prominent along with cognitive symptoms (loss of interest, feeling hopeless). A total of 6.3% presented with severe depressive symptoms. Perceived stress levels were high (mean 4.8±3.5) with 41.0% exceeding the normative scores and highest stress rates observed amongst those with Rutherford 5-6 observed (37.8-43.4%). ( Figure ). Conclusions: As clinically relevant depressive symptoms and perceived stress are very common experiences in patients navigating a CLI diagnosis, integrated pathways that include behavioral evaluation and treatment in concert with CLI treatment goals are urgently indicated.
Abstract 14960: Mutation to Troponin Inhibitor3 Switch Domain Causes Restrictive Cardiomyopathy by Reducing Sensitivity to Beta-Adrenergic Stimulus
Authors: Jason M Duran, Maria Manso, Paul Bushway, Kerry Kao, Tsui-Min WANG, Sofie Maisel, Yusu Gu, Joshua Fong, Chao Chen, Angel Soto-Hermida, marina cruz, Wei Feng, Yoshi Cho, Julius Bogomolovas, Robert S Ross, Ju Chen, Cat A Makarewich, Andrew D McCulloch, Michael Regnier, Eric D Adler
Journal: Circulation (2022)

Introduction: Troponin inhibitor3 ( TNNI3 ) is a thin-filament protein that regulates contraction of thick filaments. The role of the switch domain of TNNI3 (aa147-163), which interacts with the calcium-binding pocket of troponin C, is poorly defined. Pathogenic mutations to the switch domain cause restrictive cardiomyopathy in humans, but no therapies exist that address the underlying problem of this mutation at the sarcomeric level. Further, few models of genetic restrictive cardiomyopathy exist to aid in development of new therapies. Hypothesis: Substitution of alanine with valine at position 157 (A157V) in the switch domain of TNNI3 causes restrictive cardiomyopathy by blunting response to adrenergic stimulus. Methods: A known pathogenic mutation to the TNNI3 switch domain (A157V) was identified in a family of patients with cardiomyopathy and restrictive features. A mutant knock-in mouse homozygous for this mutation (A157V) was generated using CRISPR-Cas9 and used to elucidate the function of the switch domain. Results: Compared to wild type controls (WT), mutant A157V mice demonstrate significant restrictive features on invasive hemodynamics that worsen with age but do not show evidence of systolic dysfunction or hypertrophy on echocardiography. Heart size and myocyte cross-sectional area were significantly smaller in mutant A157V mice compared to WT controls. Molecular dynamics simulations revealed reduced TNNI3 activation in response to PKA-mediated phosphorylation at serine23/24. Isolated myocytes from A157V mice demonstrated impaired relaxation, lower peak systolic calcium and delayed reuptake of calcium into the sarcoplasmic reticulum compared to WT controls. Conclusions: The A157V mutation to the switch domain of TNNI3 , a critical regulatory domain that interacts with the calcium binding pocket of troponin C, causes diastolic dysfunction by impairing responsiveness to PKA-mediated phosphorylation of S23/24. This mouse model recapitulates the key restrictive features of human disease and could be used as a platform to study future targeted therapeutics for thin filament cardiomyopathy.
Abstract 15228: Manganese-Enhanced MRI (MEMRI) Determines the Mechanistic Efficacy of Exosome Therapy in a Porcine Myocardial Infarction Model
Authors: Hiroyuki Takashima, Gentaro Ikeda, Chunli Zhao, Nathan Bayardo, Connor O'Brien, Phillip C Yang
Journal: Circulation (2022)

Introduction: Transplantation of exosomes from mesenchymal stem cells (MSCs) and induced pluripotent stem cell derived cardiomyocytes (iCMs) improves heart function after myocardial infarction (MI). However, imaging methods have not been established to assess the mechanism of these treatments. Contrast imaging with gadolinium delayed-enhancement MRI (DEMRI) allows non-specific quantification of myocardial fibrosis. In contrast, MEMRI demonstrates active uptake of manganese into intracellular space by the viable cardiomyocytes via L-type calcium channel. MEMRI delineates the level of cellular metabolism and identifies the recovery of the injured but viable cardiomyocytes in the peri-infarct region (PIR). Hypothesis: MEMRI reflects the mechanistic efficacy of cell therapy. Methods: Yorkshire swine were subject to percutaneous proximal left anterior descending artery occlusion for 1 hour. Ten 500ul injections containing 5 x 10 11 exosomes isolated from MSCs and iCMs were delivered transendocardially to the PIR. Four weeks after injury, left ventricular ejection fraction (LVEF), and myocardial scar/viability were measured. DEMRI and MEMRI delineated the PIR to quantify the effects of exosomes. Results: The LVEF of PBS (control), MSC-exosome, and iCM-exosome groups was 18.66% ± 4.23, 27.46% ± 6.16, and 29.5% ± 3.96*, respectively (*p&lt;0.05). The % contrast enhancement by DEMRI over total LV volume were 29.38% ± 4.86, 28.76% ± 5.02, and 29.58% ± 5.55, respectively. Meanwhile, the % contrast nulling (CN, non-viable) by MEMRI were 20.51% ± 3.86, 9.53% ± 1.99, and 7.31% ± 2.62*, respectively (*p&lt;0.01). mRNA seq of the porcine myocardium and subsequent gene ontology and KEGG analyses demonstrated significant differential gene expression of iCM-exosome group related to calcium regulation (adenylate cyclase 7, 3.30-fold change) and sarcoplasmic reticulum calcium ion transport (chemokine receptor 5, 3.15-fold change). Conclusions: The % CN reduction of MEMRI reflects improved cardiomyocyte metabolism and calcium handing by exosome therapy. The underlying mechanism and functional improvement are identified by MEMRI.
Abstract 14914: Post-Acute Sequelae of SARS-CoV-2 and Mortality Among Individuals With Breakthrough Infections in Alabama
Authors: Javier Jurado Velez, Nita Kanney, Sadeep Shrestha, Bertha Hidalgo
Journal: Circulation (2022)

Introduction: While breakthrough SARS-CoV-2 infections were expected among vaccinated individuals, less is known about the incidence of post-acute SARS-CoV-2 sequelae (PASC) and mortality among vaccinated individuals. Methods: A retrospective analysis of Alabama Health System electronic health record (EHR) data was performed for 4,274 individuals with vaccination, clinical, medical, and mortality information between December 2020 and December 2021. The study population consisted of patients who had documented evidence of vaccination (e.g., two doses of Pfizer-BioNTech, two doses of Moderna, or a single dose of Janssen/Johnson &amp; Johnson vaccines). Results: Out of 4,274 individuals with EHR data in our cohort, 2,177 were female (51%), with a mean age equal to 56 ± 16.2; 1,245 individuals had received one or more doses of a COVID-19 vaccine. There were 640 COVID-19 related deaths, of which were 265 women (41%), 487 (76%) had obesity/overweight, and 133 patients (21%) that had an organ transplant or had a history of cancer. A greater percentage of unvaccinated individuals had documented COVID-19 deaths compared to individuals who were vaccinated (N=57, 5% and 583, 19%, respectively). The odds of mortality were lower among those who were vaccinated, compared to those who were unvaccinated (OR = 0.2, 95% CI = 0.15, 0.27). Sensitivity analyses showed that mortality among vaccinated individuals comprised of 6% (13) of patients with 1 dose, 5% (42) of patients with 2 doses, and &lt;1% (2) of patients with 3 doses. One hundred and eighteen individuals had a PASC diagnosis, with 57% (67) of patients having received at least 1 dose. PASC occurred in 6% (13) of patients with 1 dose, 10% (84) of patients with 2 doses, and 3% (6) of patients with 3 doses. The odds of having PASC were higher among those vaccinated, compared to those unvaccinated (OR = 3.32, 95% CI = 2.29, 4.81). Among those who were vaccinated and had PASC (N=67), a greater proportion were female than male (69% compared to 31%, respectively). Conclusions: At least 1 dose of a COVID-19 vaccine provided a lower odds of mortality in individuals with a breakthrough infection; however, in our population, vaccinated individuals had equal odds of post-acute SARS-CoV-2 sequelae (PASC) as unvaccinated individuals.
Abstract 14329: Impact of Low Body Mass Index on Cardiac Tamponade During Catheter Ablation for Atrial Fibrillation
Authors: Reina Tonegawa-Kuji, Michikazu Nakai, Koshiro Kanaoka, Kengo Kusano, Yoshitaka Iwanaga, Teiichi Yamane
Journal: Circulation (2022)

Background: Cardiac tamponade is a potentially fatal complication of catheter ablation for atrial fibrillation (AF). The risk of cardiac tamponade during AF ablation in underweight patients has never been investigated. This study aimed to evaluate the impact of body mass index (BMI) on the prediction of cardiac tamponade during AF ablation. Methods: Patients who underwent catheter ablation for AF between April 2016 and March 2018 were analyzed using a Japanese nationwide claims database, the Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination (JROAD-DPC). Mixed-effects multivariable logistic regression analysis was performed to investigate the association between BMI and cardiac tamponade. Results: A total of 59,807 hospitalizations (median age: 67 [60-73], 29% women) with catheter ablation for AF were analyzed. Cardiac tamponade occurred in 657 patients (1.1%). Multivariable analysis revealed that being underweight (BMI &lt;18.5) was associated with an increased risk of cardiac tamponade (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.05-2.02) when compared with having a normal weight (BMI 18.5-&lt;25) (Figure). Other predictors of an increased risk of cardiac tamponade were age &gt;75 years, female sex, history of heart failure, hypertension, diabetes, and dialysis treatment. In a stratified analysis by ablation technique, being underweight was associated with an increased risk of cardiac tamponade in the radiofrequency ablation group, but it was not a significant predictor in the cryoballoon ablation group. Conclusions: In this analysis of a large nationwide database of patients with AF who underwent ablation, being underweight was independently associated with an increased risk of cardiac tamponade during AF ablation. Clinicians should consider the higher risk of cardiac tamponade in the underweight population and take appropriate measures to reduce this risk.
Abstract 15193: Coronary Ectasia in Patients With Thoracic Aortic Aneurysm
Authors: Rishi Tripathi, Mohammad Zafar, Bulat A Ziganshin, John A Elefteriades, Elissa Altin
Journal: Circulation (2022)

Introduction: Coronary ectasia is identified on coronary angiography in 1-5% of cases; however, its etiology, associations, and prognostic significance are poorly characterized Methods: In a large retrospective cohort of thoracic aortic aneurysm (TAA) patients, we identified rates of coronary ectasia and the presence of aortic aneurysm and bicuspid aortic valve. Two reviewers independently assessed coronary angiograms for the presence of coronary ectasia, defined as a diameter 1.5 times larger than the adjacent healthy reference segment or an absolute diameter &gt; 4.5 mm. Results: Of the 474 TAA patients assessed, coronary ectasia was identified in 87 (18.4%). Amongst patients with coronary ectasia, 59 (67.8%) had isolated thoracic aortic aneurysms [11 (18.6%) had aortic root involvement, 46 (78.0%) had ascending aortic involvement, and 2 (3.4%) had descending aortic involvement]. Further, 28 patients had aneurysms across vascular beds [5 (17.9%) had root and ascending aortic involvement; 11 (39.3%) had combined ascending and descending aortic involvement; 9 (32.1%) had both thoracic and abdominal aortic aneurysms and 3 (10.8%) had diffuse aneurysmal disease involving other beds including intracranial, iliac and distal aortic aneurysms]. Additionally, 16 (18.39%) patients with coronary ectasia were found to have a bicuspid aortic valve where fused right and left coronary cusps were the most common anatomic variant [7 (43.75%) patients]. Of the 87 ectasia patients, there were no major adverse cardiac events including rupture of the ectatic coronary segments or related thrombosis or myocardial infarction during the mean follow-up period of 5 years. Conclusion: This study identifies that coronary ectasia occurs in TAA patients at a rate higher than expected for the general population, demonstrating a potential association between these conditions. At 5-year follow up, the presence of coronary ectasia is not associated with any major adverse cardiac events.
Abstract 15138: Lower Extremity Arterial Calcification: Association With Walking Impairment in Patients With Peripheral Arterial Disease
Authors: Eleanor T Rimmerman, Surina A Patel, Ting-Heng Chou, Sarah A Janse, Adam J Bobbey, Said A Atway, Michael R Go, Mitchel R Stacy
Journal: Circulation (2022)

Introduction: Increasing prevalence of arterial calcium in the lower extremities of patients with peripheral arterial disease (PAD) is associated with worsening clinical outcomes. Calcium burden can be detected in patients using standard imaging methods. However, quantitative evaluation of calcium burden in specific arteries of the leg in PAD patients is uncommon in the clinical setting, and the association between quantified levels of vessel-specific calcium burden and functional capacity in PAD remains understudied. We hypothesized that x-ray computed tomography (CT) imaging could quantify calcium mass of the superficial femoral (SFA) and popliteal artery and CT-derived measures of calcium burden would be associated with walking impairment scores. Methods: Healthy controls (n=8) and patients with PAD (n=44) underwent CT imaging of the legs. Calcium mass was quantified from CT images by manual segmentation of the combined SFA and popliteal artery from axial images, with established calcium defined as arterial segments with CT image intensities &gt;130 Hounsfield units. To assess functional capacity, the Walking Impairment Questionnaire (WIQ) was administered at the time of imaging. Univariate and multivariate analyses were performed to assess the association between calcium measures and walking impairment scores. Results: WIQ scores for distance, speed, and stairs significantly differed between healthy controls and PAD patients (all scores, p&lt;0.0001). Calcium mass values for the SFA-popliteal artery were significantly higher in PAD patients versus healthy controls (p=0.0005). In univariate analysis, WIQ scores for distance (p=0.004), speed (p&lt;0.001), and stairs (p=0.002) were significantly associated with calcium mass of the SFA-popliteal artery. Associations between WIQ scores and SFA-popliteal artery calcium mass remained significant after adjusting for age and body mass index in multivariate analyses. Conclusions: These results suggest that calcium burden above the knee is significantly associated with walking impairment. Implementation of arterial calcium scoring for the lower extremities in PAD patients may provide novel insight into the relationships between calcium burden, PAD symptoms, and functional limitations.